129 research outputs found

    Human Papilloma Virus (HPV) status, P16INK4a and p53 overexpression in epithelial malignant and borderline ovarian neoplasms

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    This investigation is the first to evaluate simultaneously human papilloma virus (HPV) status, p16(INK4a), and p53 immunoreactivity in epithelial ovarian neoplasms. The results were analyzed and correlated with histological type, histological grade, and survival of patients. Subtypes considered are papillary serous and mucinous. Polymerase chain reaction (PCR) analysis, performed in our previous study, had already demonstrated a small number of HPV-positive epithelial ovarian neoplasms. No significant correlation was found between the presence of HPV DNA and subtypes of ovarian neoplasms; thus, HPV cannot be considered responsible for epithelial ovarian neoplasm. Since p16 immunoreactivity was present in many other HPV-negative cases of epithelial ovarian neoplasms, this study suggests that p16 overexpression in some neoplasms of the female genital tract is not related to HPV carcinogenesis. A higher p53 expression rate observed between borderline and malignant serous tumors and between serous and mucinous neoplasms can confirm a recent dualistic model of ovarian carcinogenesis. According to this theory, low-grade serous carcinomas (serous intraepithelial carcinomas, serous borderline neoplasm, and ovarian mucinous neoplasms) (type I tumors) develop from mutations of KAS and BRAF, while high-grade serous carcinomas (type II tumors) develop from mutation of p53. In malignant neoplasms, for univariate analysis, patient survival seems to be related to p53, strong and diffuse p16 overexpression, and the stage of development of neoplasms at the diagnosis. In multinomial logistic regression, used to evaluate the role of staging, grading, p16 and p53 immunopositivity as predictor variables of unfavorable outcome of the disease, only p16 positivity was significantly related to the poor prognosis of the cancer

    Luspatercept improves hemoglobin levels and blood transfusion requirements in a study of patients with b-thalassemia

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    b-thalassemia is a hereditary disorder with limited approved treatment options; patients experience anemia and its complications, including iron overload. The study aim was to determine whether luspatercept could improve anemia and disease complications in patients with b-thalassemia. This open-label, nonrandomized, uncontrolled study consisted of a 24-week dose-finding and expansion stage (initial stage) and a 5-year extension stage, currently ongoing. Sixty-four patients were enrolled; 33 were non\u2013transfusion dependent (mean hemoglobin, <10.0 g/dL; <4 red blood cell [RBC] units transfused per 8 weeks), and 31 were transfusion dependent (\u20214 RBC units per 8 weeks). Patients received 0.2 to 1.25 mg/kg luspatercept subcutaneously every 21 days for \u20215 cycles (dose-finding stage) and 0.8 to 1.25 mg/kg (expansion cohort and 5-year extension). The primary end point was erythroid response, defined as hemoglobin increase of \u20211.5 g/dL from baseline for \u202114 consecutive days (without RBC transfusions) for non\u2013transfusion-dependent patients or RBC transfusion burden reduction \u202120% over a 12-week period vs the 12 weeks before treatment for transfusion-dependent patients. Eighteen non\u2013transfusion-dependent patients (58%) receiving higher dose levels of luspatercept (0.6-1.25 mg/kg) achieved mean hemoglobin increase \u20211.5 g/dL over \u202114 days vs baseline. Twenty-six (81%) transfusion-dependent patients achieved \u202120% reduction in RBC transfusion burden. The most common grade 1 to 2 adverse events were bone pain, headache, and myalgia. As of the cutoff, 33 patients remain on study. In this study, a high percentage of b-thalassemia patients receiving luspatercept had hemoglobin or transfusion burden improvements. These findings support a randomized clinical trial to assess efficacy and safety. This study was registered at www.clinicaltrials.gov as #NCT01749540 and #NCT02268409

    Paclitaxel 175 or 225 mg per Meters Squared With Carboplatin in Advanced Ovarian Cancer: A Randomized Trial

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    Purpose To analyze the effect of different doses of paclitaxel with fixed doses of carboplatin in the treatment of ovarian cancer. Patients and Methods Patients with histologically confirmed epithelial ovarian cancer, International Federation of Gynecology and Obstetrics stages IIB to IV, were eligible for this randomized, multicenter study. Women were randomly assigned to treatment with (1) carboplatin at the dose (in milligrams) corresponding to the following formula: target area under the free carboplatin plasma concentration versus time curve (AUC) 6 (glomerular filtration rate 25) mg/m2 (AUC6) plus paclitaxel 175 mg/m2 for six cycles every 21 days or (2) carboplatin AUC6 plus paclitaxel 225 mg/m2 for six cycles every 21 days. A total of 502 women entered the study. Results Pathologic complete response was documented in 132 patients (63.8%) in the 175 mg/m2 group and in 127 cases (55.7%) in the 225 mg/m2 group ( 2 P .090). The 4-year progression-free survival rate was 41.5% (SE 3.5) in the 175-mg group and 39.2% (SE 3.5) in the 225-mg group. The corresponding 4-year survival rates were 46.2% (based on 115 deaths) and 47.3% (based on 113 deaths), respectively. Conclusion This randomized trial suggests that paclitaxel 175 mg/m2 plus carboplatin AUC6 is the schedule with a more favorable profile than paclitaxel 225 mg/m2 plus carboplatin AUC6

    Prevalence of Hepatitis B, C, HIV and syphilis markers among refugees in Bari, Italy

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    <p>Abstract</p> <p>Background</p> <p>The aim of this study was to assess the prevalence of Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) serological markers and the prevalence of VDRL positive subjects in a population of refugees of various nationalities, living in the Asylum Seeker Centre in Bari Palese, Southern Italy.</p> <p>Methods</p> <p>The study was carried out in the period May-July 2008 and recruited only voluntarily enrolled healthy refugees. HBsAg, anti-HBc, anti-HCV and anti-HIV virus antibodies were detected. VDRL syphilis screening was also carried out on the serum samples.</p> <p>Results</p> <p>A total of 529 refugees, 442 males and 87 females, aged between 7 and 52 years, were studied. Of these, 510 were from Africa and 19 from Asia.</p> <p>Forty-four individuals (8.3%) were HBsAg positive and 241 (45.6%) were anti-HBc positive. A total of 24 (4.5%) individuals were anti-HCV positive. Eight asylum seekers (1.5%) were HIV positive. VDRL tests were performed on 269 subjects and 4 (1.5%) were positive. 12.3% of the study population had serological markers of chronic and transmissible infections with potential blood-borne or sexual transmission.</p> <p>Conclusions</p> <p>In Italy, a suitable protocol is necessary for the early diagnosis of infectious diseases on entering Asylum Centres, so allowing the adoption of prevention measures to safeguard the health of the individuals, the residents and workers in the Centres and the general population.</p

    Применение метода контрольных возмущений для определения характерных узлов присоединения комплексной нагрузки при расчетах динамической устойчивости

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    Рассматривается влияние способа замещения комплексной нагрузки на характер электромеханических переходных процессов в электрических системах (ЭС) от действия больших возмущений. Показано, что установить общие рекомендации относительно способа замещения нагрузки в сложных ЭС затруднительно. Предлагается для опреде­ления характерных узлов нагрузки, оказывающих существенное влияние на характер динамического перехода, применять известный метод контрольных возмущений. Приводятся результаты сравнительных расчетов с использованием предлагаемой методики

    Doxorubicin versus doxorubicin and cisplatin in endometrial carcinoma: definitive results of a randomised study (55872) by the EORTC Gynaecological Cancer Group

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    Background: Combination chemotherapy yields better response rates which do not always lead to a survival advantage. The aim of this study was to investigate whether the reported differences in the efficacy and toxicity of monotherapy with doxorubicin (DOX) versus combination therapy with cisplatin (CDDP) in endometrial adenocarcinoma lead to significant advantage in favour of the combination. Patients and methods: Eligible patients had histologically-proven advanced and/or recurrent endometrial adenocarcinoma and were chemo-naïve. Treatment consisted of either DOX 60 mg/m2 alone or CDDP 50 mg/m2 added to DOX 60 mg/m2, every 4 weeks. Results: A total of 177 patients were entered and median follow-up is 7.1 years. The combination DOX-CDDP was more toxic than DOX alone. Haematological toxicity consisted mainly of white blood cell toxicity grade 3 and 4 (55% versus 30%). Non-haematological toxicity consisted mainly of grade 3 and 4 alopecia (72% versus 65%) and nausea/vomiting (36 % versus 12%). The combination DOX-CDDP provided a significantly higher response rate than single agent DOX (P <0.001). Thirty-nine patients (43%) responded on DOX-CDDP [13 complete responses (CRs) and 26 partial responses (PRs)], versus 15 patients (17%) on DOX alone (8 CR and 7 PR). The median overall survival (OS) was 9 months in the DOX-CDDP arm versus 7 months in the DOX alone arm (Wilcoxon P = 0.0654). Regression analysis showed that WHO performance status was statistically significant as a prognostic factor for survival, and stratifying for this factor, treatment effect reaches significance (hazard ratio = 1.46, 95% confidence interval 1.05-2.03, P = 0.024). Conclusions: In comparison to single agent DOX, the combination of DOX-CDDP results in higher but acceptable toxicity. The response rate produced is significantly higher, and a modest survival benefit is achieved with this combination regimen, especially in patients with a good performance statu

    Managing chronic myeloid leukemia for treatment-free remission: A proposal from the GIMEMA CML WP

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    Several papers authored by international experts have proposed recommendations on the management of BCR-ABL11 chronic myeloid leukemia (CML). Following these recommendations, survival of CML patients has become very close to normal. The next, ambitious, step is to bring as many patients as possible into a condition of treatment-free remission (TFR). The Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA; Italian Group for Hematologic Diseases of the Adult) CML Working Party (WP) has developed a project aimed at selecting the treatment policies that may increase the probability of TFR, taking into account 4 variables: the need for TFR, the tyrosine kinase inhibitors (TKIs), the characteristics of leukemia, and the patient. A Delphi-like method was used to reach a consensus among the representatives of 50 centers of the CML WP. A consensus was reached on the assessment of disease risk (EUTOS Long Term Survival [ELTS] score), on the definition of the most appropriate age boundaries for the choice of first-line treatment, on the choice of the TKI for first-line treatment, and on the definition of the responses that do not require a change of the TKI (BCR-ABL1 ≤10% at 3 months, ≤1% at 6 months, ≤0.1% at 12 months, ≤0.01% at 24 months), and of the responses that require a change of the TKI, when the goal is TFR (BCR-ABL1 &gt;10% at 3 and 6 months, &gt;1% at 12 months, and &gt;0.1% at 24 months). These suggestions may help optimize the treatment strategy for TFR

    Adjuvant chemotherapy vs radiotherapy in high-risk endometrial carcinoma: results of a randomised trial

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    Patients with high-risk endometrial carcinoma (stage IcG3, IIG3 with myometrial invasion >50%, and III) receive adjuvant therapy after surgery but it is not clear whether radiotherapy (RT) or chemotherapy (CT) is better. We randomly assigned 345 patients with high-risk endometrial carcinoma to adjuvant CT (cisplatin (50 mg m−2), doxorubicin (45 mg m−2), cyclophosphamide (600 mg m−2) every 28 days for five cycles, or external RT (45–50 Gy on a 5 days week−1 schedule). The primary end points were overall and progression-free survival. After a median follow-up of 95.5 months women in the CT group as compared with the RT group, had a no significant hazard ratio (HR) for death of 0.95 (95% confidence interval (CI), 0.66–1.36; P=0.77) and a nonsignificant HR for event of 0.88 (95% CI, 0.63–1.23; P=0.45). The 3, 5 and 7-year overall survivals were 78, 69 and 62% in the RT group and 76, 66 and 62% in the CT group. The 3, 5 and 7-year progression-free survivals were, respectively, 69, 63 and 56 and 68, 63 and 60%. Radiotherapy delayed local relapses and CT delayed metastases but these trends did not achieve statistical significance. Overall, both treatments were well tolerated. This trial failed to show any improvement in survival of patients treated with CT or the standard adjuvant radiation therapy. Randomised trials of pelvic RT combined with adjuvant cytotoxic therapy compared with RT alone are eagerly awaited
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